The ability of transcription factors to reprogram the identity of cells is usually very limited and hampers our ability to generate cells types for various different applications. In this grant proposal, entitled Generating neurons through cellular reprogramming, we propose to conduct genetic screens in the nematode C. elegans that will identify factors that normally act to prevent the ability of transcription factors to reprogram cellular identities. In preliminary work, two such reprogramming brakes were identified. Further genetic screens may reveal more of these reprogramming inhibitors and help us better understand the plasticity of cellular, and specifically neuronal identity. This grant proposal makes specific use of the C. elegans model system as a gene discovery tool. PUBLIC HEALTH RELEVANCE: This research proposal studies the molecular mechanisms that underlie the reprogramming of the identity of individual cells. Conceptually, the reprogramming of cellular identity has enormous potential for cell replacement therapies of various human diseases, including neurological diseases, in which individual cells are lost and in which one wishes to replace those cells with intact, reprogrammed cells.